Evolutionary History of the Plant Pathogenic Bacterium Xanthomonas axonopodis

Deciphering mechanisms shaping bacterial diversity should help to build tools to predict the emergence of infectious diseases. Xanthomonads are plant pathogenic bacteria found worldwide. Xanthomonas axonopodis is a genetically heterogeneous species clustering, into six groups, strains that are collectively pathogenic on a large number of plants. However, each strain displays a narrow host range. We address the question of the nature of the evolutionary processes – geographical and ecological speciation – that shaped this diversity. We assembled a large collection of X. axonopodis strains that were isolated over a long period, over continents, and from various hosts. Based on the sequence analysis of seven housekeeping genes, we found that recombination occurred as frequently as point mutation in the evolutionary history of X. axonopodis. However, the impact of recombination was about three times greater than the impact of mutation on the diversity observed in the whole dataset. We then reconstructed the clonal genealogy of the strains using coalescent and genealogy approaches and we studied the diversification of the pathogen using a model of divergence with migration. The suggested scenario involves a first step of generalist diversification that spanned over the last 25 000 years. A second step of ecology-driven specialization occurred during the past two centuries. Eventually, secondary contacts between host-specialized strains probably occurred as a result of agricultural development and intensification, allowing genetic exchanges of virulence-associated genes. These transfers may have favored the emergence of novel pathotypes. Finally, we argue that the largest ecological entity within X. axonopodis is the pathovar.     

Urinary Interleukin-8 Is a Biomarker of Stress in Emergency Physicians,Especially with Advancing Age — The JOBSTRESS* Randomized Trial

Background

Emergency physicians are exposed to greater stress during a 24-hour shift (24 hS) than a 14-hour night shift (14 hS), with an impact lasting several days. Interleukin-8 (IL-8) is postulated to be a chronic stress biomarker. However, no studies have tracked IL-8 over several shifts or used it for monitoring short-term residual stress. The IL-8 response to the shifts may also increase with age. Conveniently, IL-8 can be measured non-intrusively from urine.

Methods

We conducted a shifts-randomized trial comparing 17 emergency physicians’ urinary IL-8 levels during a 24 hS, a 14 hS, and a control day (clerical work on return from leave). Mean levels of IL-8 were compared using a Wilcoxon matched-pairs test. Independent associations of key factors including shifts, stress, and age with IL-8 levels were further assessed in a multivariable generalized estimating equations model.

Results

Mean urinary IL-8 levels almost doubled during and after a 24 hS compared with a 14 hS or a control day. Furthermore, IL-8 levels failed to return to control values at the end of the third day after the shift despite a rest day following the 24 hS. In the multivariable model, engaging in a 24 hS, self-reported stress, and age were independently associated with higher IL-8 levels. A 24 hS significantly increased IL-8 levels by 1.9 ng (p = .007). Similarly, for every unit increase in self-reported stress, there was a 0.11 ng increase in IL-8 levels (p = .003); and for every one year advance in age of physicians, IL-8 levels also increased by 0.11 ng (p = .018).

Conclusion

The 24 hS generated a prolonged response of the immune system. Urinary IL-8 was a strong biomarker of stress under intensive and prolonged demands, both acutely and over time. Because elevated IL-8 levels are associated with cardiovascular disease and negative psychological consequences, we suggest that emergency physicians limit their exposure to 24 hS, especially with advancing age.     

Elevational adaptation and plasticity in seedling phenology of temperate deciduous tree species

Phenological events, such as the initiation and the end of seasonal growth, are thought to be under strong evolutionary control because of their influence on tree fitness. Although numerous studies highlighted genetic differentiation in phenology among populations from contrasting climates, it remains unclear whether local adaptation could restrict phenological plasticity in response to current warming. Seedling populations of seven deciduous tree species from high and low elevations in the Swiss Alps were investigated in eight common gardens located along two elevational gradients from 400 to 1,700 m. We addressed the following questions: are there genetic differentiations in phenology between populations from low and high elevations, and are populations from the upper elevational limit of a species’ distribution able to respond to increasing temperature to the same extent as low-elevation populations? Genetic variation of leaf unfolding date between seedlings from low and high populations was detected in six out of seven tree species. Except for beech, populations from high elevations tended to flush later than populations from low elevations, emphasizing that phenology is likely to be under evolutionary pressure. Furthermore, seedlings from high elevation exhibited lower phenological plasticity to temperature than low-elevation provenances. This difference in phenological plasticity may reflect the opposing selective forces involved (i.e. a trade-off between maximizing growing season length and avoiding frost damages). Nevertheless, environmental effects were much stronger than genetic effects, suggesting a high phenological plasticity to enable tree populations to track ongoing climate change, which includes the risk of tracking unusually warm springs followed by frost.     

N1,N3-disubstituted uracils as nonnucleoside inhibitors of HIV-1 reverse transcriptase

A series of phenyloxyethyl and cinnamyl derivatives of substituted uracils were synthesized and found to exhibit potent activity against HIV-RT and HIV replication in cell culture. In general, the cinnamyl derivatives proved superior to the phenyloxyethyl derivatives, however 1-[2-(4-methylphenoxy)ethyl]-3-(3,5-dimethylbenzyl)uracil (19) exhibited the highest activity (EC₅₀ = 0.27 μM) thus confirming that the 3-benzyluracil fragment in the NNRTI structure can be regarded as a functional analogue of the benzophenone pharmacophore typically found in NNRTIs.     

Disentangling the effects of global climate and regional land-use change on the current and future distribution of mangroves in South Africa

The mangrove distribution in South Africa is fragmented and restricted to small forest patches occupying only 16 % of the estuaries within the current range. In this study we used species distribution models to test (1) whether the absence of mangrove forest and its species (Avicennia marina, Bruguiera gymnorrhiza and Rhizophora mucronata) within their current range is driven by climate or by climate combined with human or geomorphic perturbation and (2) how climate change may potentially affect the latitudinal limit of the mangrove forests and its species in South Africa. We used three modelling techniques (generalized linear models, generalized additive models and gradient boosting machines) and a set of three climate-based predictive variables (minimum air temperature of the coldest month, waterbalance and growing-degree days) combined separately with an index of human or geomorphic perturbation. Climate variables for the future projections were derived from two general circulation models driven by two socio-economic scenarios (A2a and B2a). Within the range of the mangrove forest, the fragmented distribution of the mangroves in South Africa was not explained by our set of climate variables alone. The index of human perturbations slightly improved the predictions but the index of geomorphic perturbation did not. Climate change will create climatically suitable sites for the mangrove forest and the two species A. marina and B. gymnorrhiza beyond their current limits, but model outcomes did not agree on the future potential distribution of R. mucronata. We were able to successfully predict range limits and to detect future climatically suitable sites beyond the current limits. Factors controlling mangrove distribution within its range are still to be identified although absences were partly explained by human perturbations.     

Germline Mutations in the Polyposis-Associated Genes BMPR1A,SMAD4, PTEN,MUTYH and GREM1 Are Not Common in Individuals with Serrated Polyposis Syndrome

Background

Recent reports have observed that individuals with serrated polyps, some of whom meet the clinical diagnostic criteria for Serrated Polyposis Syndrome (SPS), are among those who carry germline mutations in genes associated with polyposis syndromes including; (1) genes known to underlie hamartomatous polyposes (SMAD4, BMPR1A, and PTEN), (2) MUTYH-associated polyposis and (3) GREM1 in Hereditary Mixed Polyposis Syndrome (HMPS). The aim of this study was to characterise individuals fulfilling the current WHO criteria for SPS for germline mutations in these polyposis-associated genes.

Methods

A total of 65 individuals with SPS (fulfilling WHO criteria 1 or 3), were recruited to the Genetics of Serrated Neoplasia study between 2000 and 2012, through multiple Genetics or Family Cancer Clinics within Australia, or from the New Zealand Familial Gastrointestinal Cancer Service. Individuals with SPS were tested for coding mutations and large deletions in the PTEN, SMAD4, and BMPR1A genes, for the MUTYH variants in exons 7 (Y179C) and 13 (G396D), and for the duplication upstream of GREM1.

Results

We found no variants that were likely to be deleterious germline mutations in the SPS cases in the PTEN, SMAD4, and BMPR1A genes. A novel variant in intron 2 (c.164+223T>C) of PTEN was identified in one individual and was predicted by in silico analysis to have no functional consequences. One further individual with SPS was found to be mono-allelic for the MUTYH G396D mutation. No individuals carried the recently reported duplication within GREM1.

Conclusions

Genes involved in the gastrointestinal hamartomatous polyposis, Hereditary Mixed Polyposis Syndrome and MUTYH-associated polyposis syndromes are not commonly altered in individuals with SPS.     

Haemosporidian Parasites of Antelopes and Other Vertebrates from Gabon,Central Africa

Re-examination, using molecular tools, of the diversity of haemosporidian parasites (among which the agents of human malaria are the best known) has generally led to rearrangements of traditional classifications. In this study, we explored the diversity of haemosporidian parasites infecting vertebrate species (particularly mammals, birds and reptiles) living in the forests of Gabon (Central Africa), by analyzing a collection of 492 bushmeat samples. We found that samples from five mammalian species (four duiker and one pangolin species), one bird and one turtle species were infected by haemosporidian parasites. In duikers (from which most of the infected specimens were obtained), we demonstrated the existence of at least two distinct parasite lineages related to Polychromophilus species (i.e., bat haemosporidian parasites) and to sauropsid Plasmodium (from birds and lizards). Molecular screening of sylvatic mosquitoes captured during a longitudinal survey revealed the presence of these haemosporidian parasite lineages also in several Anopheles species, suggesting a potential role in their transmission. Our results show that, differently from what was previously thought, several independent clades of haemosporidian parasites (family Plasmodiidae) infect mammals and are transmitted by anopheline mosquitoes.